O Transplante Alogênico de Células-Tronco (TCTH) é uma terapia potencialmente curativa para Leucemia Linfoblástica Aguda (LLA). Um grande desafio continua sendo a Mortalidade Relacionada ao Transplante (TRM), embora a taxa de mortalidade tenha diminuído. Nos países em desenvolvimento, pesquisas anteriores sobre TCTH destacaram que a mortalidade precoce está relacionada a resultados clínicos inferiores. É crucial identificar os fatores envolvidos na mortalidade precoce para melhores desfechos e cura. Diante disso, este estudo tem como objetivo investigar os fatores de risco associados à mortalidade precoce após TCTH para LLA em centros brasileiros. Trata-se de uma coorte retrospectiva de pacientes com LLA ou ambígua leucemia de linhagem acima de 16 anos que realizaram o primeiro TCTH em 5 centros brasileiros entre janeiro de 2007 e dezembro de 2017. A Mortalidade Precoce (MP) foi definida como morte dentro de 100 dias a partir do TCTH. A análise multivariada foi realizada por meio de regressão logística, baseada no critério de informação de Akaike para seleção do modelo. Um valor de p < 0,05 foi considerado estatisticamente significativo. 275 pacientes foram incluídos, a mediana de idade foi de 31 anos e 58,5% eram do sexo masculino. O cromossomo Ph foi relatado em 35% e a maioria dos pacientes estava em primeira remissão completa (66%). Doador aparentado HLA-idêntico (MSD), doador não-aparentado HLA idêntico (MUD), doador não-aparentado com Mismatch (MMUD), doador haploidêntico, e cordão umbilical foram relatados em 53%, 19%, 9%, 19% e 5%, respectivamente. A mediana de idade dos doadores foi de 31 anos e 54,4% eram do sexo masculino. A taxa de MP foi de 24,4%. Na análise univariada, os fatores que estiveram estatisticamente relacionados a MP foram: fonte de células (p < 0,001), KPS basal (p = 0,03), sexo (feminino vs. masculino, 16,7 vs. 27,9%, p = 0,03), status Ph-positivo (p = 0,03), doença refratária (p = 0,015), fonte de sangue de cordão umbilical (p = 0,01) e idade do doador (p = 0,08). Não houve diferença entre as taxas de MP comparando os centros públicos e privados (24,5 vs. 19%, p = 0,463). O melhor modelo multivariado incluiu gênero, estado de Ph, tipo de doador e idade do doador como variáveis finais para MP. Nesta coorte, o status Ph-positivo (OR = 2,83), a idade do doador (OR = 1,05) e o uso de MUD (OR = 3,68) foram independentemente associados à MP. Em relação à causa de MP, 69% foram relacionados à infecção, e 19,5% a DECH agudo. A MP foi maior em pacientes Ph-positivos sem remissão molecular importante (BCR-ABL ≥ 0,1% – 40% vs. 3,6%, p = 0,008). A incidência cumulativa de DECH aguda no dia 100 foi de 48,3% pela análise competitiva. Apenas 3 de 62 mortes no grupo MP foram devido à recidiva da doença. As demais mortes foram secundárias à infecção bacteriana (52%), seguido por DECH aguda (17,8%) e infecção fúngica (8,9%). Este estudo representa a maior análise no Brasil para avaliar precocemente a mortalidade nesse grupo de pacientes. Embora as características gerais dos pacientes foram semelhantes a análises prévias, a taxa de MP deste estudo foi maior do que em outras coortes. Notavelmente, fatores relacionados ao transplante, como a idade e o tipo do doador, além do status Ph-positivo, foram associados com MP, superando fatores previamente conhecidos como intensidade de condicionamento e o uso de TBI. Esses achados podem ajudar a melhorar a seleção de doadores no Brasil.
The treatment and evolution of B-cell non-Hodgkin lymphoma (B-NHL) has undergone important changes in the last years with the emergence of targeted therapies, such as monoclonal antibodies, small molecules, antibody-drug conjugates, and bispecific antibodies. Nevertheless, a significant portion of patients remains refractory or relapsed (R/R) to the new therapeutic modalities, representing thus an unmet medical need. The use of CAR-T cells for the treatment of B-NHL patients has shown to be a promising therapy with impressive results in patients with R/R disease. The expectations are as high as the imminent approval of CAR-T cell therapy in Brazil, which it is expected to impact the prognosis of R/R B-NHL. The aim of this manuscript is to offer a consensus of specialists in the field of onco-hematology and cellular therapy, working in Brazil and United States, in order to discuss and offer recommendations in the present setting of the use of CAR-T cells for patients with B-NHL.
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely indicated as a therapy for patients with malignant and non-malignant hematological pathologies. One of the major causes of late morbidity and mortality of allogeneic HSCT is chronic graft-versus-host disease (cGVHD), occurring in 30-70% of the patients. Clinical manifestations of cGVHD can be restricted to a single organ or site or can be disseminated, with deep impact on patient's quality of life. Our center started its activities in August 1996, and since January 2009, HSCT data is reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). As of August 31, 2017, 1,597 patients were included in the CIBMTR. Our data management team is composed by a data analyst, a data control assistant and a nurse. Over the years, we have worked diligently to keep up with the form updates made by the CIBMTR. As an international center, it was necessary to translate the forms to the Portuguese language. The nurse completes the post-HSCT follow-up forms and, based on the evolution and results of the patients' exams, prepares periodic reports, following the CIBMTR's update sequence. During the elaboration of those forms, characteristics that may indicate a possible GVHD are searched. Diagnosing cGVHD in early phase may be tricky, so it is necessary to follow the evolution. After the collection of all information, the data is weekly confirmed by one of the HSCT physicians. The use of those forms aims to ensure the best possible quality of the data. Objective: As our service does not have electronic medical records, we aimed to demonstrate how the development of an adhesive and permanent tag for classification and graduation of cGVHD (Figure 1), streamlines the preparation process of the information that is reported to the CIBMTR, reduces errors, and improves data reliability, acting as a facilitator tool. Materials and Methods: Adhesive tags were developed, separated by the main organs affected by cGVHD, which have all the necessary information for the proper graduation, following NIH criteria. Those tags are available in all sectors of our HSCT Service. During medical appointment, after diagnosing cGVHD or new progressions, the physicians fill and glue the tag at the medical record. The presence of this tool stimulates the medical team to record the information in a more detail way. Results: The number of cases to be checked in the weekly meetings with our physician team decreased after the implementation of the adhesive tags, contributing with greater agility in finalizing the reports and sending the data. Conclusion: When the physician fills the adhesive tags during the medical appointment, increases guarantee of reliability of the information, allowing the data manager to report the data with greater security, without needing knowledge in the medical area.
'/%3e%3cpath id='l' d='M-26.25 0h52.5v-12h-40.5v-16h33v-12h-33v-11H25v-12h-51.25z'/%3e%3cpath id='k' d='M-31.5 0h12v-48l14 48h11l14-48V0h12v-70H14L0-22l-14-48h-17.5z'/%3e%3cpath id='b' fill-rule='evenodd' d='M0 0a31.5 35 0 0 0 0-70A31.5 35 0 0 0 0 0m0-13a18.5 22 0 0 0 0-44 18.5 22 0 0 0 0 44'/%3e%3cpath id='d' fill-rule='evenodd' d='M-31.5 0h13v-26h28a22 22 0 0 0 0-44h-40zm13-39h27a9 9 0 0 0 0-18h-27z'/%3e%3cpath id='n' d='M-15.75-22C-15.75-15-9-11.5 1-11.5s14.74-3.25 14.75-7.75c0-14.25-46.75-5.25-46.5-30.25C-30.5-71-6-70 3-70s26 4 25.75 21.25H13.5c0-7.5-7-10.25-15-10.25-7.75 0-13.25 1.25-13.25 8.5-.25 11.75 46.25 4 46.25 28.75C31.5-3.5 13.5 0 0 0c-11.5 0-31.55-4.5-31.5-22z'/%3e%3cuse xlink:href='%23a' id='o' transform='scale(31.5)'/%3e%3cuse xlink:href='%23a' id='p' transform='scale(26.25)'/%3e%3cuse xlink:href='%23a' id='r' transform='scale(21)'/%3e%3cuse xlink:href='%23a' id='q' transform='scale(15)'/%3e%3cuse xlink:href='%23a' id='s' transform='scale(10.5)'/%3e%3cg id='m'%3e%3cclipPath id='c'%3e%3cpath d='M-31.5 0v-70h63V0zM0-47v12h31.5v-12z'/%3e%3c/clipPath%3e%3cuse xlink:href='%23b' clip-path='url(%23c)'/%3e%3cpath d='M5-35h26.5v10H5z'/%3e%3cpath d='M21.5-35h10V0h-10z'/%3e%3c/g%3e%3cg id='h'%3e%3cuse xlink:href='%23d'/%3e%3cpath d='M28 0c0-10 0-32-15-32H-6c22 0 22 22 22 32'/%3e%3c/g%3e%3cg id='a' fill='%23fff'%3e%3cg id='f'%3e%3cpath id='e' d='M0-1v1h.5' transform='rotate(18 0 -1)'/%3e%3cuse xlink:href='%23e' transform='scale(-1 1)'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='rotate(72)'/%3e%3cuse xlink:href='%23f' transform='rotate(-72)'/%3e%3cuse xlink:href='%23f' transform='rotate(144)'/%3e%3cuse xlink:href='%23f' transform='rotate(216)'/%3e%3c/g%3e%3c/defs%3e%3crect width='100%25' height='100%25' x='-50%25' y='-50%25' fill='%23009b3a'/%3e%3cpath fill='%23fedf00' d='M-1743 0 0 1113 1743 0 0-1113z'/%3e%3ccircle r='735' fill='%23002776'/%3e%3cclipPath id='g'%3e%3ccircle r='735'/%3e%3c/clipPath%3e%3cpath fill='%23fff' d='M-2205 1470a1785 1785 0 0 1 3570 0h-105a1680 1680 0 1 0-3360 0z' clip-path='url(%23g)'/%3e%3cg fill='%23009b3a' transform='translate(-420 1470)'%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(-7)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(-4)'/%3e%3cuse xlink:href='%23i' y='-1697.5' transform='rotate(-1)'/%3e%3cuse xlink:href='%23j' y='-1697.5' transform='rotate(2)'/%3e%3cuse xlink:href='%23k' y='-1697.5' transform='rotate(5)'/%3e%3cuse xlink:href='%23l' y='-1697.5' transform='rotate(9.75)'/%3e%3cuse xlink:href='%23d' y='-1697.5' transform='rotate(14.5)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(17.5)'/%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(20.5)'/%3e%3cuse xlink:href='%23m' y='-1697.5' transform='rotate(23.5)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(26.5)'/%3e%3cuse xlink:href='%23j' y='-1697.5' transform='rotate(29.5)'/%3e%3cuse xlink:href='%23n' y='-1697.5' transform='rotate(32.5)'/%3e%3cuse xlink:href='%23n' y='-1697.5' transform='rotate(35.5)'/%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(38.5)'/%3e%3c/g%3e%3cuse xlink:href='%23o' x='-600' y='-132'/%3e%3cuse xlink:href='%23o' x='-535' y='177'/%3e%3cuse xlink:href='%23p' x='-625' y='243'/%3e%3cuse xlink:href='%23q' x='-463' y='132'/%3e%3cuse xlink:href='%23p' x='-382' y='250'/%3e%3cuse xlink:href='%23r' x='-404' y='323'/%3e%3cuse xlink:href='%23o' x='228' y='-228'/%3e%3cuse xlink:href='%23o' x='515' y='258'/%3e%3cuse xlink:href='%23r' x='617' y='265'/%3e%3cuse xlink:href='%23p' x='545' y='323'/%3e%3cuse xlink:href='%23p' x='368' y='477'/%3e%3cuse xlink:href='%23r' x='367' y='551'/%3e%3cuse xlink:href='%23r' x='441' y='419'/%3e%3cuse xlink:href='%23p' x='500' y='382'/%3e%3cuse xlink:href='%23r' x='365' y='405'/%3e%3cuse xlink:href='%23p' x='-280' y='30'/%3e%3cuse xlink:href='%23r' x='200' y='-37'/%3e%3cuse xlink:href='%23o' y='330'/%3e%3cuse xlink:href='%23p' x='85' y='184'/%3e%3cuse xlink:href='%23p' y='118'/%3e%3cuse xlink:href='%23r' x='-74' y='184'/%3e%3cuse xlink:href='%23q' x='-37' y='235'/%3e%3cuse xlink:href='%23p' x='220' y='495'/%3e%3cuse xlink:href='%23r' x='283' y='430'/%3e%3cuse xlink:href='%23r' x='162' y='412'/%3e%3cuse xlink:href='%23o' x='-295' y='390'/%3e%3cuse xlink:href='%23s' y='575'/%3e%3c/svg%3e)
